Clara cell 16-kd protein downregulates TH2 differentiation of human naive neonatal T cells

BackgroundLevels of the Clara cell 16-kd protein (CC16) are lower in plasma and bronchoalveolar lavage fluid from adults with asthma relative to those seen in healthy control subjects, and CC16 inhibits the TH2 cytokine production from murine T cells.ObjectiveWe sought to determine the plasma levels of CC16 in infants and to investigate whether CC16 might inhibit the TH2 cytokine production from neonatal T cells.MethodsCord blood and blood samples at 4, 18, and 36 months of age were taken from 64 children prospectively, and CC16 levels were analyzed in plasma. Cord monocyte-derived dendritic cells (DCs) were pulsed with birch allergen extract alone or together with CC16 or prostaglandin D2 receptor inhibitors, after which autologous naive CD4+ T cells were added to the DCs. The production of IL-5, IL-13, and IFN-γ was measured by means of ELISA and flow cytometry.ResultsThe plasma levels of CC16 in children peaked at 4 months. CC16 did not directly affect the cytokine production from human TH2 cells. However, CC16 inhibited birch pollen extract–stimulated TH2 differentiation of naive T cells through the DC. Inhibition of the prostaglandin D2 receptors did not consistently result in suppressed TH2 differentiation.ConclusionThe production of CC16 seems to peak early in life, and CC16 has an inhibitory effect on TH2 cell differentiation from human infants by affecting DCs.Clinical implicationsCC16 is an immunoregulatory protein, and its inhibitory effect on TH2 cell differentiation might be of importance in the pathogenesis of allergy in infants.